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Diffusion-weighted imaging: basic concepts and application in cerebral stroke and head trauma.

Diffusion-weighted imaging (DWI) of the brain represents a new imaging technique that extends imaging from depiction of neuroanatomy to the level of function and physiology. DWI measures a fundamentally different physiological parameter compared with conventional MRI. Image contrast is related to differences in the diffusion rate of water molecules rather than to changes in total tissue water. DWI can reveal pathology in cases where conventional MRI remains unremarkable. DWI has proven to be highly sensitive in the early detection of acute cerebral ischemia and seems promising in the evaluation of traumatic brain injury. DWI can differentiate between lesions with decreased and increased diffusion. In addition, full-tensor DWI can evaluate the microscopic architecture of the brain, in particular white matter tracts, by measuring the degree and spatial distribution of anisotropic diffusion within the brain. This article reviews the basic concepts of DWI and its application in cerebral ischemia and traumatic brain injury.

Artifacts↗

Phenotype and genotype heterogeneity in autosomal dominant polycystic kidney disease.

It is now clear that mutations of at least two genetic loci can lead to autosomal dominant polycystic kidney disease (ADPKD). We have compared the clinical features of ADPKD caused by mutations at the PKD1 locus (linked to the alpha-globin complex on chromosome 16) with those of disease not linked to the locus (non-PKD1). We identified 18 families (285 affected members) with mutations at PKD1 and 5 families (49 affected individuals) in which involvement of this locus could be dismissed. Non-PKD1 patients lived longer than PKD1 patients (median survival 71.5 vs 56.0 years), had a lower risk of progressing to renal failure (odds ratio 0.35, 95% CI 0.13-0.92), were less likely to have hypertension (odds ratio adjusted for age and family of origin 0.29, 0.11-0.80), were diagnosed at an older age (median 69.1 vs 44.8 years), and had fewer renal cysts at the time of diagnosis. Although most of the PKD1 families were ascertained through clinics treating patients with renal impairment, no non-PKD1 family was identified through this source. Non-PKD1 ADPKD has a much milder phenotype than that linked to PKD1. Partly as a result of this difference in severity, the reported prevalence of this genotype is probably an underestimate.

Adolescent↗

The effect of clonidine on auditory P300.

Auditory evoked potential recordings were done on 14 normal subjects during baseline conditions as well as after oral administration of 0.2 mg of clonidine or placebo. P300 amplitude and latency measurements were obtained from 28 electrodes and analyzed. Clonidine resulted in a decrease in P300 amplitude, which was most marked in the occipital and left parieto-temporal regions. This effect was significant even after controlling for the sedative side effect of clonidine. P300 was unaffected by clonidine. These data suggest the possible use of clonidine-induced changes in P300 amplitude as an index of central noradrenergic responsiveness.

Adult↗

Brain asymmetry: facts and fallacies in statistical inference.

In a recent article, C. M. Clark, R. Kessler, and R. Margolin (1985, Brain and Cognition, 4, 7-12) argue that standard statistical tests should not be applied to measures of regional cerebral metabolism. They offer no evidence that such measures uniquely escape the mathematical foundations of statistical inference but, instead, merely note the definitional relations among various descriptive and inferential statistics. They falsely claim that these relations invalidate conclusions drawn from statistical tests, and in making this claim, they commit several quite serious logical fallacies. These fallacies are examined.

Brain Mapping↗

Reduction of ocular artefacts in source current density brain mappings by ARX2 filtering.

Sweep by sweep analysis of event-related potentials (ERP) of the human scalp represents a reliable tool for both the diagnosis of neurologic diseases and the study of the central nervous system during cognitive tasks. The off-line procedure based on stochastic parametric identification and filtering herewith described, allows an accurate analysis of single-sweep ERP and a drastic reduction of ocular artefacts variously propagating through the skull. Moreover, the spatial distribution of the recorded ERP in bidimensional form was enhanced by using the Laplacian operator in order to get an estimate of the source current density (SCD) flow from the skull into the scalp. Complete single-trial signals were filtered according to an autoregressive model of signal generation with 2 exogenous inputs (ARX2). The ARX2 procedure models the recorded signal as the sum of three signals: (a) the background EEG activity, modelled as an autoregressive process driven by a white noise; (b) a filtered version of a reference signal carrying the average information contained in each sweep; (c) a signal due to the ocular artefact propagation. The evaluation of the effect of artefact suppression on those channels close to the eyes was compared with standard ordinary least squares method (OLS) based on a linear model of the influence of EOG on ERP. Finally, the better results obtainable through ARX filtering on sweep-by-sweep brain mappings are also presented.

Adult↗

Effect of working memory on evaluation-related frontocentral negativity.

Recent results suggest that a negative ERP potential emerges not only on error trials, but is also found after correct responses. There is broad evidence that this component is generated in the anterior cingulate cortex (ACC). The present study aimed to explore the influence of working memory demands on the evaluation process probably reflected by the negative potential. To this purpose, a modified continuous performance task (CPT) was used, with variations of the delay between cues and imperative stimuli. Data were analyzed using conventional averaging techniques as well as source localization with LORETA (low resolution brain electromagnetic tomography). Results suggest a significant effect of working memory delay on the amplitude of the post-response negative ERP component. Its source was located in the anterior cingulate cortex, with the exact location being dependent upon working memory demands. The results support the notion of a general response evaluation system reflected by a post-response negative component. The findings of a working memory dependent modification of this potential suggest a functional link between the medial frontal cortex and the lateral frontal regions primarily involved in working memory processing.

Adult↗

Full-band EEG (FbEEG): an emerging standard in electroencephalography.

While enormous resources have been recently invested into the development of a variety of neuroimaging techniques, the bandwidth of the clinical EEG, originally set by trivial technical limitations, has remained practically unaltered for over 50 years. An increasing amount of evidence shows that salient EEG signals are observed beyond the bandwidth of the routine clinical EEG, which is typically around 0.5-50 Hz. Physiological and pathological EEG activity ranges at least from 0.01 Hz to several hundred Hz, as demonstrated in recordings of spontaneous activity in the immature human brain, as well as during epileptic seizures, or various kinds of cognitive tasks and states in the adult brain. In the present paper, we will review several arguments leading to the conclusion that elimination of the lower (infraslow) or higher (ultrafast) bands of the EEG frequency spectrum in routine EEG leads to situations where salient and physiologically meaningful features of brain activity are ignored. Recording the full, physiologically relevant range of frequencies is readily attained with commercially available direct-current (DC) coupled amplifiers, which have a wide dynamic range and a high sampling rate. Such amplifiers, combined with appropriate DC-stable electrode-skin interface, provide a genuine full-band EEG (FbEEG). FbEEG is mandatory for a faithful, non-distorted and non-attenuated recording, and it does not have trade-offs that would favor any frequency band at the expense of another. With the currently available electrode, amplifier and data acquisition technology, FbEEG is likely to become the standard approach for a wide range of applications in both basic science and in the clinic.

Brain↗

Recent progress in targeting the Raf/MEK/ERK pathway with inhibitors in cancer drug discovery.

Since the discovery that activating mutations of the Ras GTPase were associated with 30% or more of human cancers, the RAF/MEK/ERK pathway has been the focus of intense drug discovery effort. Within the new class of molecularly targeted anti-cancer agents progressing through the late stages of clinical development, BAY 43-9006 and PD0325901 have shown considerable promise.

Animals↗

Rapid confirmation and revision of the primary structure of bovine serum albumin by ESIMS and Frit-FAB LC/MS.

Incorrectness of the amino acid sequence of bovine serum albumin (BSA) was suggested from the observed molecular weight of BSA obtained by electrospray ionization mass spectrometry (ESIMS). Lack of a tyrosine residue in the position of 156th was found rapidly, by the combination of frit-fast atom bombardment mass spectrometry/liquid chromatography (Frit-FAB LC/MS), automated Edman degradation and tandem mass spectrometry (MS). Then it turned out that BSA is composed of 583 amino acid residues, and that its average molecular weight is not 66267.1, and it is corrected to 66430.3. Moreover the amino acid sequence of the positions of 94th and 95th was corrected to -QE- by using automated Edman degradation method.

Amino Acid Sequence↗

Lead system transformation for pooling of body surface map data: a surface Laplacian approach.

In this paper, a method is described to transform Body Surface Map (BSM) data from one lead system to that of another. This enables pooling of BSM data between different centres. The transformation tool is based upon Laplacian interpolation. It is evaluated by inspecting transformations from lead systems having few leads to one having many leads.

Body Surface Potential Mapping↗

Linkage and association: basic concepts.

Many investigators are turning their efforts to dissecting the etiology of complex traits. The primary tools for gene discovery, localization, and functional analysis are linkage and association studies. While the conceptual underpinnings of these approaches have long been known, advances in recent decades in molecular genetics, in the development of efficient computational algorithms, and in computing power have enabled the large-scale application of these methods. Here, we review the biological basis of linkage and association among loci and the common methods used to assess these relationships with respect to observed phenotypes. We further consider the two most common approaches--genome scans and candidate gene studies--especially their respective strengths, weaknesses, and resource requirements. Finally, we highlight some of the major challenges that arise from these investigative approaches and those that are inherent in the nature of complex traits. The chapters that follow elaborate on many of these topics.

Chromosome Mapping↗

Deciphering Arabidopsis thaliana gene neighborhoods through bibliographic co-citations.

In the framework of genome annotation, scientific literature is obviously the major source of biological knowledge. The aim of the work described in this paper is to exploit this source of data for the model plant Arabidopsis thaliana. The first step has consisted in constituting a relevant bibliographic references dataset for plant genomic research. Genes co-citations have then been systematically annotated in this reference dataset, starting from the simple idea that if genes are cited in the same publication, they must probably share some related functional properties. In order to deal with the synonymous gene name problem, a gene name reference list has been constituted starting from A. thaliana SwissProt entries. This list was used to build clusters of co-cited genes by a single linkage procedure such that any gene in a given cluster possesses at least one co-cited partner in the same cluster. Analysis of the clusters demonstrate the biological consistency of this approach, with only very few fortuitous links. As an example, a cluster including genes related to flowering time is more deeply described in the paper. Finally, a graphical representation of each cluster was performed, which provides a convenient way to retrieve the genes (the nodes of the graphs) and the references in which they were co-cited (the edges of the graphs). All the results can be accessed at the URL http://chlora.Igi.infobiogen.fr:1234/bib_arath/.

Arabidopsis↗

Amplification refractory mutation system for prenatal diagnosis and carrier assessment in cystic fibrosis.

The amplification refractory mutation system (ARMS) has been applied to prenatal diagnosis and carrier detection of cystic fibrosis. The nucleotide sequence of both alleles of the PstI restriction fragment length polymorphism at the KM19 locus, which displays linkage disequilibrium with cystic fibrosis, has been determined. ARMS enables direct analysis of alleles of this polymorphism in DNA isolated from chorionic villus biopsy or white blood cells.

Alleles↗

Primary ablation of atrial flutter and atrial fibrillation.

Direct treatment of atrial flutter and atrial fibrillation--that is, attempting to prevent arrhythmia recurrences by ablating atrial tissue--has been a challenge because of uncertainty about the location of optimal target tissues as well as the amount of atrial tissue requiring destruction to effect cure. Advances have yielded success rates for ablation of the common form of atrial flutter comparable to those for other types of supraventricular tachycardia and provide reason for optimism about the use of catheter techniques, to treat atrial fibrillation definitively. This article discusses some of these advances as well as the current status of catheter ablation for atrial flutter and atrial fibrillation and, finally, what the future may bring.

Animals↗